It is well known that mineral deficiencies such as hypokalemia and hypomagnesemia can occur for a variety of dietary or physiological reasons and often result from long term therapy with drugs such as thiazides and loop diuretics. Hypokalemia and hypomagnesemia can cause variety of unpleasant or dangerous symptoms including cardiac arrhythymias, weakness, fatigue and muscle cramps.
While the need for potassium and magnesium supplementation is well recognized, no combination supplements known to date have been completely successful. Potassium is known to cause irritation and/or ulceration in the gastric tract when taken orally, so combinations of salts such as the granulation described in UK Patent 1,356,096, which provides both potassium and magnesium in immediate release form, are likely to promote gastric upset.
Other known formulations wherein the release of both the potassium and magnesium are controlled, e.g. those described in U.S. Pat. No. 4,104,370 and UK patent 1,356,097, tend to promote the same gastric problems, but for the opposite reason. That is, wax-matrix formulations such as disclosed in the cited patents may not disintegrate rapidly or completely, causing high local concentrations of potassium injurious to the gastric tract. These wax-matrix tablets, as well as other controlled release formulations such as that described in German patent 2,132,923, wherein enteric coated capsules are disclosed, (which capsules in effect become immediate release formulations when the coating and capsule dissolve, thereby presenting the problems associated with non-controlled release potassium salts) further present the possibility of reduced bioavailability of magnesium. Magnesium is absorbed from the gastrointestinal tract in the region of the upper small bowel by means of an active process closely related to the transport system for calcium. Therefore, the use of magnesium in a controlled-release or enteric-release form would be inappropriate due to the reduced biavailability. Moreover, unlike potassium, the controlled release of magnesium is unnecessary since magnesium salts are not associated with gastrointestinal irritation and ulceration.
Furthermore, the above cited patents may not provide therapeutic doses of both potassium and magnesium. The dosages in the formulation in the cited patents range from a low of 0.25 to a high of 15 meq. for magnesium and from a low of 0.4 to a high of 10 meq. for potassium. However, the recommended daily dietary allowance for magnesium in adults is 25 to 33.4 meq (milliequivalent). The daily dose of magnesium required to prevent depletion in patients receiving diuretics has not yet been established, while a daily dose of 20 meq of potassium is typically used for the prevention of hypokalmia.